While it has been shown that increasing NO levels can be therapeutic for a number of conditions, the biochemical mechanism of nitrite reduction to NO, and thereby increasing NO levels, is poorly understood. Nitrite reduction in vivo occurs through different pathways, however efficiency of nitrite reduction in vivo is difficult to control or augment. Some agents can facilitate such reduction, such as ascorbic acid, but do so weakly. Strong biocompatible agents to stimulate nitrite reduction to NO are not available in current technology.
Nitrite levels in an organism are important to know, but nitrite is difficult to measure in solution.
While proper diagnosis is an important factor in timely appropriate treatment of underlying disease, non-critical limb ischemic peripheral artery disease (PAD) and critical limb ischemia (CLI) can be difficult to distinguish and accurately diagnose, beyond the limited clinical diagnosis of ankle brachial index or claudication.